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c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling

The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specific...

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Autores principales: Fontana, Xavier, Hristova, Mariya, Da Costa, Clive, Patodia, Smriti, Thei, Laura, Makwana, Milan, Spencer-Dene, Bradley, Latouche, Morwena, Mirsky, Rhona, Jessen, Kristjan R., Klein, Rüdiger, Raivich, Gennadij, Behrens, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392945/
https://www.ncbi.nlm.nih.gov/pubmed/22753894
http://dx.doi.org/10.1083/jcb.201205025
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author Fontana, Xavier
Hristova, Mariya
Da Costa, Clive
Patodia, Smriti
Thei, Laura
Makwana, Milan
Spencer-Dene, Bradley
Latouche, Morwena
Mirsky, Rhona
Jessen, Kristjan R.
Klein, Rüdiger
Raivich, Gennadij
Behrens, Axel
author_facet Fontana, Xavier
Hristova, Mariya
Da Costa, Clive
Patodia, Smriti
Thei, Laura
Makwana, Milan
Spencer-Dene, Bradley
Latouche, Morwena
Mirsky, Rhona
Jessen, Kristjan R.
Klein, Rüdiger
Raivich, Gennadij
Behrens, Axel
author_sort Fontana, Xavier
collection PubMed
description The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyrosine kinase, were identified as novel direct c-Jun target genes. Genetic inactivation of Ret specifically in neurons resulted in regeneration defects without affecting motoneuron survival and, conversely, administration of recombinant GDNF and Artemin protein substantially ameliorated impaired regeneration caused by c-Jun deficiency. These results reveal an unexpected function for c-Jun in SCs in response to axonal injury, and identify paracrine Ret signaling as an important mediator of c-Jun function in SCs during regeneration.
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spelling pubmed-33929452013-01-09 c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling Fontana, Xavier Hristova, Mariya Da Costa, Clive Patodia, Smriti Thei, Laura Makwana, Milan Spencer-Dene, Bradley Latouche, Morwena Mirsky, Rhona Jessen, Kristjan R. Klein, Rüdiger Raivich, Gennadij Behrens, Axel J Cell Biol Research Articles The AP-1 transcription factor c-Jun is a master regulator of the axonal response in neurons. c-Jun also functions as a negative regulator of myelination in Schwann cells (SCs) and is strongly reactivated in SCs upon axonal injury. We demonstrate here that, after injury, the absence of c-Jun specifically in SCs caused impaired axonal regeneration and severely increased neuronal cell death. c-Jun deficiency resulted in decreased expression of several neurotrophic factors, and GDNF and Artemin, both of which encode ligands for the Ret receptor tyrosine kinase, were identified as novel direct c-Jun target genes. Genetic inactivation of Ret specifically in neurons resulted in regeneration defects without affecting motoneuron survival and, conversely, administration of recombinant GDNF and Artemin protein substantially ameliorated impaired regeneration caused by c-Jun deficiency. These results reveal an unexpected function for c-Jun in SCs in response to axonal injury, and identify paracrine Ret signaling as an important mediator of c-Jun function in SCs during regeneration. The Rockefeller University Press 2012-07-09 /pmc/articles/PMC3392945/ /pubmed/22753894 http://dx.doi.org/10.1083/jcb.201205025 Text en © 2012 Fontana et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Fontana, Xavier
Hristova, Mariya
Da Costa, Clive
Patodia, Smriti
Thei, Laura
Makwana, Milan
Spencer-Dene, Bradley
Latouche, Morwena
Mirsky, Rhona
Jessen, Kristjan R.
Klein, Rüdiger
Raivich, Gennadij
Behrens, Axel
c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title_full c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title_fullStr c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title_full_unstemmed c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title_short c-Jun in Schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
title_sort c-jun in schwann cells promotes axonal regeneration and motoneuron survival via paracrine signaling
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3392945/
https://www.ncbi.nlm.nih.gov/pubmed/22753894
http://dx.doi.org/10.1083/jcb.201205025
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